Few SARS-CoV-2 infections detected in Newfoundland and Labrador in the absence of Public Health Laboratory-based confirmation

Abstract

Objective To assess the incidence of COVID-19 infection in the absence of a confirmatory test in persons suspecting they contracted COVID-19 and elucidate reasons for their belief. Methods We recruited persons with a confirmed COVID-19 diagnosis and persons who believed they may have contracted COVID-19 between December, 2019 and April, 2021 into a study of immunity against SARS-CoV-2. An intake questionnaire captured their perceived risk factors for exposure and symptoms experienced, including symptom duration and severity. ELISA testing against multiple SARS-CoV-2 antigens was done to detect antibodies against SARS-CoV-2. No participant had received COVID-19 vaccination prior to the time of testing. Results The vast majority of study subjects without Public Health confirmation of infection had no detectable antibodies against SARS-CoV-2. Suspected infection with SARS-CoV-2 generally involved experiencing symptoms common to many other respiratory infections. Unusually severe or persistent symptoms often supported suspicion of infection with SARS-CoV-2 as did travel or contact with travelers from outside Newfoundland and Labrador. Rare cases in which antibodies against SARS-CoV-2 were detected despite negative results of Public Health testing for SARS-CoV-2 RNA involved persons in close contact with confirmed cases. Conclusions Broad public awareness and declaration of pandemic status in March, 2020 contributed to the perceived risk of contracting COVID-19 in Newfoundland and Labrador from late 2019 to April 2021 and raised expectation of its severity. Serological testing is useful to diagnose past infection with SARS-CoV-2 to accurately estimate population exposure rates.

Moderate to severe SARS-CoV-2 infection primes vaccine-induced immunity more effectively than asymptomatic or mild infection

“…A questionnaire addressing previous testing history and reasons for suspecting infection with SARS-CoV-2 was administered at study intake and peripheral blood was collected from study subjects by forearm venipuncture at ∼three-month intervals after obtaining written informed consent in accordance with the Declaration of Helsinki. Persons with previous RT-PCR-confirmed SARS-CoV-2 infection or who suspected previous infection, which was subsequently confirmed serologically, were recruited to study immune responses against SARS-CoV-2 19 . Thirty-five individuals with confirmed infection who continued in the study and received 2 doses of a COVID-19 vaccine were categorized blindly as experiencing asymptomatic (score = 0) mild (score = 1), moderate (score = 2) or severe (score = 3) COVID-19 based on the duration and intensity of their self-reported symptoms.…”

“…Plates were washed six times with wash buffer followed by the addition of TMB substrate (Sigma-Aldrich; 100 μL/well). Reactions were stopped after 20 minutes of color development using an equal volume of 1 M H 2 SO 4 (Sigma-Aldrich) and optical density (OD) was read on a BioTek synergy HT plate reader at 450 nm 19 . A human IgG 1 neutralizing Ab against RBD, mAb SAD-S35 (AcroBiosystems, Newark, DE, USA), was used at 16 ng/mL for SMT1-1-coated conditions and 8 ng/mL (100 μL/well) for RBD-coated conditions on each plate to reach OD ~1 and OD readings from test plasma samples were normalized to these values.…”

“…Cases of persons completely lacking Ab responses against SARS-CoV-2 who recover from infection with no need for medical intervention empirically illustrate the importance of cellular immunity in controlling SARS-CoV-2 infection 19 – 23 . Other cases indicating that occult exposure to SARS-CoV-2 induces a cellular immune response that enables viral clearance with no development of symptoms or induction of humoral immunity also imply a key role for cellular immunity 24 – 26 .…”

Characteristics of Vaccine- and Infection-Induced Systemic IgA Anti-SARS-CoV-2 Spike Responses

“…The investigation was conducted following guidelines outlined in the Canadian Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. The study’s participants are part of an ongoing research cohort at Memorial University of Newfoundland and Labrador, and all subjects within this research study were selected based on prior suspicion of SARS-CoV-2 infection or confirmation with reverse-transcriptase polymerase chain reaction (RT-PCR) [ 17 ]. In accordance with the Declaration of Helsinki, written informed consent was obtained for the collection of whole blood.…”

Hybrid immunity elicits potent cross-variant ADCC against SARS-CoV-2 through a combination of anti-S1 and S2 antibodies

“…Thirty-one individuals with confirmed infection who continued in the study and received 2 doses of a COVID-19 vaccine were matched with 40 individuals with no previous infection history who had received 2 doses of a COVID 19-vaccine (Table 1). Asymptomatic participants were identified through Public Health surveillance and contact tracing after contact with RT-PCR-confirmed cases or through serological testing for anti-S and anti-N protein IgG Abs (60). Most participants enrolled following the first wave of COVID-19 and infections were attributed to ancestral Wuhan-Hu-1 SARS-CoV-2.…”